Q8CJG0 · AGO2_MOUSE
- ProteinProtein argonaute-2
- GeneAgo2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids860 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. Regulates lymphoid and erythroid development and function, and this is independent of endonuclease activity.
Catalytic activity
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein argonaute-2
- EC number
- Short namesArgonaute2 ; mAgo2
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8CJG0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Embryonic death with a strong defect in neural tube closure and apparent cardiac failure.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 45 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000194058 | 1-860 | Protein argonaute-2 | |||
Sequence: MYSGAGPVLASPAPTTSPIPGYAFKPPPRPDFGTTGRTIKLQANFFEMDIPKIDIYHYELDIKPEKCPRRVNREIVEHMVQHFKTQIFGDRKPVFDGRKNLYTAMPLPIGRDKVELEVTLPGEGKDRIFKVSIKWVSCVSLQALHDALSGRLPSVPFETIQALDVVMRHLPSMRYTPVGRSFFTASEGCSNPLGGGREVWFGFHQSVRPSLWKMMLNIDVSATAFYKAQPVIEFVCEVLDFKSIEEQQKPLTDSQRVKFTKEIKGLKVEITHCGQMKRKYRVCNVTRRPASHQTFPLQQESGQTVECTVAQYFKDRHKLVLRYPHLPCLQVGQEQKHTYLPLEVCNIVAGQRCIKKLTDNQTSTMIRATARSAPDRQEEISKLMRSASFNTDPYVREFGIMVKDEMTDVTGRVLQPPSILYGGRNKAIATPVQGVWDMRNKQFHTGIEIKVWAIACFAPQRQCTEVHLKSFTEQLRKISRDAGMPIQGQPCFCKYAQGADSVEPMFRHLKNTYAGLQLVVVILPGKTPVYAEVKRVGDTVLGMATQCVQMKNVQRTTPQTLSNLCLKINVKLGGVNNILLPQGRPPVFQQPVIFLGADVTHPPAGDGKKPSIAAVVGSMDAHPNRYCATVRVQQHRQEIIQDLAAMVRELLIQFYKSTRFKPTRIIFYRDGVSEGQFQQVLHHELLAIREACIKLEKDYQPGITFIVVQKRHHTRLFCTDKNERVGKSGNIPAGTTVDTKITHPTEFDFYLCSHAGIQGTSRPSHYHVLWDDNRFSSDELQILTYQLCHTYVRCTRSVSIPAPAYYAHLVAFRARYHLVDKEHDSAEGSHTSGQSNGRDHQALAKAVQVHQDTLRTMYFA | ||||||
Modified residue | 2 | 3'-nitrotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 388 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 701 | 4-hydroxyproline | ||||
Sequence: P | ||||||
Modified residue | 825 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 829 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 832 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 835 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity.
Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO2 when it is engaged with a TDMD target.
Phosphorylation at Ser-388 by AKT3; leads to up-regulate translational repression of microRNA target and down-regulate endonucleolytic cleavage.
A phosphorylation cycle of C-terminal serine cluster (Ser-825-Ser-835) regulates the release of target mRNAs. Target-binding leads to phosphorylation of these residues by CSNK1A1, which reduces the affinity of AGO2 for mRNA and enables target release. The ANKRD52-PPP6C phosphatase complex dephosphorylates the residues, which primes AGO2 for binding a new target.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitous expression in 9.5 day embryos with highest levels in forebrain, heart, limb buds, and branchial arches.
Gene expression databases
Interaction
Subunit
Interacts with DICER1 through its Piwi domain and with TARBP2 during assembly of the RNA-induced silencing complex (RISC). Together, DICER1, AGO2 and TARBP2 constitute the trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Note however that the term RISC has also been used to describe the trimeric RLC/miRLC. The formation of RISC complexes containing siRNAs rather than miRNAs appears to occur independently of DICER1 (PubMed:16357216).
Interacts with AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and XRN1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is modulated under stress-induced conditions, occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with LIMD1, WTIP and AJUBA (By similarity).
Interacts with TRIM71 (PubMed:19898466, PubMed:22508726, PubMed:22735451).
Interacts with APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Interacts with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with FMR1. Interacts with ZFP36 (By similarity).
Interacts with RC3H1; the interaction is RNA independent (PubMed:25697406).
Interacts with ARB2A (PubMed:29311329).
Found in a complex composed of AGO2, CHD7 and ARB2A (PubMed:29311329).
Interacts with SND1 and SYT11 (PubMed:24882364).
Interacts with CLNK (PubMed:26009488).
Interacts with GARRE1 (By similarity).
Interacts with GRB2; this interaction is important for the formation of a ternary complex containing GRB2, AGO2 and DICER1 (By similarity).
Interacts with AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and XRN1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is modulated under stress-induced conditions, occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with LIMD1, WTIP and AJUBA (By similarity).
Interacts with TRIM71 (PubMed:19898466, PubMed:22508726, PubMed:22735451).
Interacts with APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Interacts with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with FMR1. Interacts with ZFP36 (By similarity).
Interacts with RC3H1; the interaction is RNA independent (PubMed:25697406).
Interacts with ARB2A (PubMed:29311329).
Found in a complex composed of AGO2, CHD7 and ARB2A (PubMed:29311329).
Interacts with SND1 and SYT11 (PubMed:24882364).
Interacts with CLNK (PubMed:26009488).
Interacts with GARRE1 (By similarity).
Interacts with GRB2; this interaction is important for the formation of a ternary complex containing GRB2, AGO2 and DICER1 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | Q8CJG0 | DICER1 Q9UPY3 | 2 | EBI-528299, EBI-395506 | |
XENO | Q8CJG0 | PRNP P04156 | 2 | EBI-528299, EBI-977302 | |
XENO | Q8CJG0 | PRNP P04273 | 2 | EBI-528299, EBI-986426 | |
BINARY | Q8CJG0 | Rc3h1 Q4VGL6 | 2 | EBI-528299, EBI-2366263 | |
XENO | Q8CJG0 | TNRC6C Q9HCJ0 | 3 | EBI-528299, EBI-6507625 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 230-349 | PAZ | ||||
Sequence: PVIEFVCEVLDFKSIEEQQKPLTDSQRVKFTKEIKGLKVEITHCGQMKRKYRVCNVTRRPASHQTFPLQQESGQTVECTVAQYFKDRHKLVLRYPHLPCLQVGQEQKHTYLPLEVCNIVA | ||||||
Region | 312-317 | Interaction with guide RNA | ||||
Sequence: YFKDRH | ||||||
Domain | 518-819 | Piwi | ||||
Sequence: LVVVILPGKTPVYAEVKRVGDTVLGMATQCVQMKNVQRTTPQTLSNLCLKINVKLGGVNNILLPQGRPPVFQQPVIFLGADVTHPPAGDGKKPSIAAVVGSMDAHPNRYCATVRVQQHRQEIIQDLAAMVRELLIQFYKSTRFKPTRIIFYRDGVSEGQFQQVLHHELLAIREACIKLEKDYQPGITFIVVQKRHHTRLFCTDKNERVGKSGNIPAGTTVDTKITHPTEFDFYLCSHAGIQGTSRPSHYHVLWDDNRFSSDELQILTYQLCHTYVRCTRSVSIPAPAYYAHLVAFRARYHLV | ||||||
Region | 525-567 | Interaction with guide RNA | ||||
Sequence: GKTPVYAEVKRVGDTVLGMATQCVQMKNVQRTTPQTLSNLCLK | ||||||
Region | 588-591 | Interaction with GW182 family members | ||||
Sequence: FQQP | ||||||
Region | 651-661 | Interaction with GW182 family members | ||||
Sequence: LIQFYKSTRFK | ||||||
Region | 710-711 | Interaction with guide RNA | ||||
Sequence: KR | ||||||
Region | 754-762 | Interaction with guide RNA | ||||
Sequence: HAGIQGTSR | ||||||
Region | 791-813 | Interaction with guide RNA | ||||
Sequence: YVRCTRSVSIPAPAYYAHLVAFR |
Domain
The Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH).
Sequence similarities
Belongs to the argonaute family. Ago subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length860
- Mass (Da)97,304
- Last updated2011-07-27 v3
- ChecksumA4E13C633846062C
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 65 | in Ref. 2; AAH96465 | ||||
Sequence: E → G | ||||||
Sequence conflict | 67 | in Ref. 1; BAC15767 | ||||
Sequence: C → R | ||||||
Sequence conflict | 129 | in Ref. 1; BAC15767 | ||||
Sequence: F → L | ||||||
Sequence conflict | 360 | in Ref. 1; BAC15767 | ||||
Sequence: N → D | ||||||
Sequence conflict | 563 | in Ref. 2; AAH96465 | ||||
Sequence: N → D | ||||||
Sequence conflict | 711 | in Ref. 2; AAH96465 | ||||
Sequence: R → P | ||||||
Sequence conflict | 761 | in Ref. 1; BAC15767 | ||||
Sequence: S → G |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB081472 EMBL· GenBank· DDBJ | BAC15767.1 EMBL· GenBank· DDBJ | mRNA | ||
BC096465 EMBL· GenBank· DDBJ | AAH96465.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC128379 EMBL· GenBank· DDBJ | AAI28380.1 EMBL· GenBank· DDBJ | mRNA | ||
BC129922 EMBL· GenBank· DDBJ | AAI29923.1 EMBL· GenBank· DDBJ | mRNA | ||
AK220193 EMBL· GenBank· DDBJ | BAD90378.1 EMBL· GenBank· DDBJ | mRNA |